Human Mesenchymal Precursor Cells (Stro-1) from Spinal Cord Injury Patients Improve Functional Recovery and Tissue Sparing in an Acute Spinal Cord Injury Rat Model
This study aimed to determine the potential of purified (Stro-1 + ) human mesenchymal precursor cells (hMPCs) to repair the injured spinal cord (SC) after transplantation into T-cell-deficient athymic RNU nude rats following acute moderate contusive spinal cord injury (SCI). hMPCs were isolated from...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2013-03-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/096368912X656081 |
| _version_ | 1818846990758313984 |
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| author | Stuart I. Hodgetts Paul J. Simmons Giles W. Plant |
| author_facet | Stuart I. Hodgetts Paul J. Simmons Giles W. Plant |
| author_sort | Stuart I. Hodgetts |
| collection | DOAJ |
| description | This study aimed to determine the potential of purified (Stro-1 + ) human mesenchymal precursor cells (hMPCs) to repair the injured spinal cord (SC) after transplantation into T-cell-deficient athymic RNU nude rats following acute moderate contusive spinal cord injury (SCI). hMPCs were isolated from the bone marrow (BM) stroma of SCI patients and transplanted as a suspension graft in medium [with or without immunosuppression using cyclosporin A (CsA)]. Extensive anatomical analysis shows statistically significant improvement in functional recovery, tissue sparing, and cyst reduction. We provide quantitative assessment of supraspinal projections in combination with functional outcomes. hMPC-transplanted animals consistently achieved mean BBB scores of 15 at 8 weeks postinjury. Quantitative histological staining revealed that graft-recipient animals possessed more intact spinal tissue and reduced cyst formation than controls. Fluorogold (FG) retrograde tracing revealed sparing/regeneration of supraspinal and local propriospinal axonal pathways, but no statistical differences were observed compared to controls. Immunohistochemical analysis revealed increased serotonergic (5-HT) and sensory (CGRP) axonal growth within and surrounding transplanted donor hMPCs 2 weeks posttransplantation, but no evidence of hMPC transdifferentiation was seen. Although hMPCs initially survive at 2 weeks posttransplantation, their numbers were dramatically reduced and no cells were detected at 8 weeks posttransplantation using retroviral/lentiviral GFP labeling and a human nuclear antigen (HNA) antibody. Additional immunosuppression with CsA did not improve hMPC survival or their ability to promote tissue sparing or functional recovery. We propose Stro-1 + -selected hMPCs provide (i) a reproducible source for stem cell transplantation for SC therapy and (ii) a positive host microenvironment resulting in the promotion of tissue sparing/repair that subsequently improves behavioral outcomes after SCI. Our results provide a new candidate for consideration as a stem cell therapy for the repair of traumatic CNS injury. |
| first_indexed | 2024-12-19T05:54:20Z |
| format | Article |
| id | doaj.art-6f0817da116847d0afafc21f07d49014 |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-19T05:54:20Z |
| publishDate | 2013-03-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-6f0817da116847d0afafc21f07d490142022-12-21T20:33:30ZengSAGE PublishingCell Transplantation0963-68971555-38922013-03-012210.3727/096368912X656081Human Mesenchymal Precursor Cells (Stro-1) from Spinal Cord Injury Patients Improve Functional Recovery and Tissue Sparing in an Acute Spinal Cord Injury Rat ModelStuart I. Hodgetts0Paul J. Simmons1Giles W. Plant2Eileen Bond Spinal Cord Research Laboratory, School of Anatomy and Human Biology, University of Western Australia, Perth, Western AustraliaBrown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX, USAStanford Partnership for Spinal Cord Injury and Repair, Stanford Institute for Neuro-Innovation and Translational Neurosciences and Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USAThis study aimed to determine the potential of purified (Stro-1 + ) human mesenchymal precursor cells (hMPCs) to repair the injured spinal cord (SC) after transplantation into T-cell-deficient athymic RNU nude rats following acute moderate contusive spinal cord injury (SCI). hMPCs were isolated from the bone marrow (BM) stroma of SCI patients and transplanted as a suspension graft in medium [with or without immunosuppression using cyclosporin A (CsA)]. Extensive anatomical analysis shows statistically significant improvement in functional recovery, tissue sparing, and cyst reduction. We provide quantitative assessment of supraspinal projections in combination with functional outcomes. hMPC-transplanted animals consistently achieved mean BBB scores of 15 at 8 weeks postinjury. Quantitative histological staining revealed that graft-recipient animals possessed more intact spinal tissue and reduced cyst formation than controls. Fluorogold (FG) retrograde tracing revealed sparing/regeneration of supraspinal and local propriospinal axonal pathways, but no statistical differences were observed compared to controls. Immunohistochemical analysis revealed increased serotonergic (5-HT) and sensory (CGRP) axonal growth within and surrounding transplanted donor hMPCs 2 weeks posttransplantation, but no evidence of hMPC transdifferentiation was seen. Although hMPCs initially survive at 2 weeks posttransplantation, their numbers were dramatically reduced and no cells were detected at 8 weeks posttransplantation using retroviral/lentiviral GFP labeling and a human nuclear antigen (HNA) antibody. Additional immunosuppression with CsA did not improve hMPC survival or their ability to promote tissue sparing or functional recovery. We propose Stro-1 + -selected hMPCs provide (i) a reproducible source for stem cell transplantation for SC therapy and (ii) a positive host microenvironment resulting in the promotion of tissue sparing/repair that subsequently improves behavioral outcomes after SCI. Our results provide a new candidate for consideration as a stem cell therapy for the repair of traumatic CNS injury.https://doi.org/10.3727/096368912X656081 |
| spellingShingle | Stuart I. Hodgetts Paul J. Simmons Giles W. Plant Human Mesenchymal Precursor Cells (Stro-1) from Spinal Cord Injury Patients Improve Functional Recovery and Tissue Sparing in an Acute Spinal Cord Injury Rat Model Cell Transplantation |
| title | Human Mesenchymal Precursor Cells (Stro-1) from Spinal Cord Injury Patients Improve Functional Recovery and Tissue Sparing in an Acute Spinal Cord Injury Rat Model |
| title_full | Human Mesenchymal Precursor Cells (Stro-1) from Spinal Cord Injury Patients Improve Functional Recovery and Tissue Sparing in an Acute Spinal Cord Injury Rat Model |
| title_fullStr | Human Mesenchymal Precursor Cells (Stro-1) from Spinal Cord Injury Patients Improve Functional Recovery and Tissue Sparing in an Acute Spinal Cord Injury Rat Model |
| title_full_unstemmed | Human Mesenchymal Precursor Cells (Stro-1) from Spinal Cord Injury Patients Improve Functional Recovery and Tissue Sparing in an Acute Spinal Cord Injury Rat Model |
| title_short | Human Mesenchymal Precursor Cells (Stro-1) from Spinal Cord Injury Patients Improve Functional Recovery and Tissue Sparing in an Acute Spinal Cord Injury Rat Model |
| title_sort | human mesenchymal precursor cells stro 1 from spinal cord injury patients improve functional recovery and tissue sparing in an acute spinal cord injury rat model |
| url | https://doi.org/10.3727/096368912X656081 |
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